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Genome-wide association analysis identifies susceptibility loci for migraine without aura.


ABSTRACT: Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10(-4); combined P = 7.06 × 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 × 10(-4); combined P = 1.17 × 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10(-8) and P = 0.02; combined P = 3.86 × 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.

SUBMITTER: Freilinger T 

PROVIDER: S-EPMC3773912 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Genome-wide association analysis identifies susceptibility loci for migraine without aura.

Freilinger Tobias T   Anttila Verneri V   de Vries Boukje B   Malik Rainer R   Kallela Mikko M   Terwindt Gisela M GM   Pozo-Rosich Patricia P   Winsvold Bendik B   Nyholt Dale R DR   van Oosterhout Willebrordus P J WP   Artto Ville V   Todt Unda U   Hämäläinen Eija E   Fernández-Morales Jèssica J   Louter Mark A MA   Kaunisto Mari A MA   Schoenen Jean J   Raitakari Olli O   Lehtimäki Terho T   Vila-Pueyo Marta M   Göbel Hartmut H   Wichmann Erich E   Sintas Cèlia C   Uitterlinden Andre G AG   Hofman Albert A   Rivadeneira Fernando F   Heinze Axel A   Tronvik Erling E   van Duijn Cornelia M CM   Kaprio Jaakko J   Cormand Bru B   Wessman Maija M   Frants Rune R RR   Meitinger Thomas T   Müller-Myhsok Bertram B   Zwart John-Anker JA   Färkkilä Markus M   Macaya Alfons A   Ferrari Michel D MD   Kubisch Christian C   Palotie Aarno A   Dichgans Martin M   van den Maagdenberg Arn M J M AM  

Nature genetics 20120610 7


Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10(-5) for replication testing in 2,508 individ  ...[more]

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